tbuckley/cabot-search huggingface dataset:
Integrated metagenomic and metabolomic analysis reveals distinct gut-microbiome-derived phenotypes in early-onset colorectal cancer
Authors: Cheng Kong, Lei Liang, Guang Liu, Lutao Du, Yongzhi Yang, Jianqiang Liu, Debing Shi, Xinxiang Li, Yanlei Ma
Journal: Gut (2022)

Objective The incidence of early-onset colorectal cancer (EO-CRC) is steadily increasing. Here, we aimed to characterise the interactions between gut microbiome, metabolites and microbial enzymes in EO-CRC patients and evaluate their potential as non-invasive biomarkers for EO-CRC. Design We performed metagenomic and metabolomic analyses, identified multiomics markers and constructed CRC classifiers for the discovery cohort with 130 late-onset CRC (LO-CRC), 114 EO-CRC subjects and age-matched healthy controls (97 LO-Control and 100 EO-Control). An independent cohort of 38 LO-CRC, 24 EO-CRC, 22 LO-Controls and 24 EO-Controls was analysed to validate the results. Results Compared with controls, reduced alpha-diversity was apparent in both, LO-CRC and EO-CRC subjects. Although common variations existed, integrative analyses identified distinct microbiome–metabolome associations in LO-CRC and EO-CRC. Fusobacterium nucleatum enrichment and short-chain fatty acid depletion, including reduced microbial GABA biosynthesis and a shift in acetate/acetaldehyde metabolism towards acetyl-CoA production characterises LO-CRC. In comparison, multiomics signatures of EO-CRC tended to be associated with enriched Flavonifractor plauti and increased tryptophan, bile acid and choline metabolism. Notably, elevated red meat intake-related species, choline metabolites and KEGG orthology (KO) pldB and cbh gene axis may be potential tumour stimulators in EO-CRC. The predictive model based on metagenomic, metabolomic and KO gene markers achieved a powerful classification performance for distinguishing EO-CRC from controls. Conclusion Our large-sample multiomics data suggest that altered microbiome–metabolome interplay helps explain the pathogenesis of EO-CRC and LO-CRC. The potential of microbiome-derived biomarkers as promising non-invasive tools could be used for the accurate detection and distinction of individuals with EO-CRC.
Emergence of a multidrug-resistant and virulent Streptococcus pneumoniae lineage mediates serotype replacement after PCV13: an international whole-genome sequencing study
Authors: Stephanie W Lo, Kate Mellor, Robert Cohen, Alba Redin Alonso, Sophie Belman, Narender Kumar, Paulina A Hawkins, Rebecca A Gladstone, Anne von Gottberg, Balaji Veeraraghavan, K L Ravikumar, Rama Kandasamy, Sir Andrew J Pollard, Samir K Saha, Godfrey Bigogo, Martin Antonio, Brenda Kwambana-Adams, Shaper Mirza, Sadia Shakoor, Imran Nisar, Jennifer E Cornick, Deborah Lehmann, Rebecca L Ford, Betuel Sigauque, Paul Turner, Jennifer Moïsi, Stephen K Obaro, Ron Dagan, Idrissa Diawara, Anna Skoczyńska, Hui Wang, Philip E Carter, Keith P Klugman, Gail Rodgers, Robert F Breiman, Lesley McGee, Stephen D Bentley, Carmen Muñoz-Almagro, Emmanuelle Varon
Journal: The Lancet Microbe (2022)
Longitudinal lung function and gas transfer in individuals with idiopathic pulmonary fibrosis: a genome-wide association study
Authors: Richard J Allen, Justin M Oldham, David A Jenkins, Olivia C Leavy, Beatriz Guillen-Guio, Carl A Melbourne, Shwu-Fan Ma, Jonathan Jou, John S Kim, William A Fahy, Eunice Oballa, Richard B Hubbard, Vidya Navaratnam, Rebecca Braybrooke, Gauri Saini, Katy M Roach, Martin D Tobin, Nik Hirani, Moira K B Whyte, Naftali Kaminski, Yingze Zhang, Fernando J Martinez, Angela L Linderholm, Ayodeji Adegunsoye, Mary E Strek, Toby M Maher, Philip L Molyneaux, Carlos Flores, Imre Noth, R Gisli Jenkins, Louise V Wain
Journal: The Lancet Respiratory Medicine (2022)
Treatment of Streptococcal Endocarditis With a Single Daily Dose of Ceftriaxone Sodium for 4 Weeks
Authors: Patrick Francioli
Journal: JAMA (1992)

<h3>Objective.</h3> —To evaluate the efficacy and safety of ceftriaxone sodium in the treatment of streptococcal endocarditis. <h3>Design.</h3> —An open, multicenter, noncomparative study with a follow-up of patients for 4 months to 5 years. <h3>Setting.</h3> —Internal medicine wards and outpatient clinics of hospitals of various sizes in three European countries. <h3>Patients.</h3> —Fifty-nine patients with defined criteria for streptococcal endocarditis. <h3>Intervention.</h3> —Ceftriaxone sodium administered at a once-daily dose of 2 g for 4 weeks. <h3>Main Outcome Measures.</h3> —Clinical outcome and microbiological cure rate. <h3>Results.</h3> —Among the 59 patients, 55 completed the treatment and were followed up for 4 months to 5 years. No patients showed evidence of relapse. Treatment was completely uneventful in 42 patients (71%). A cardiac valve was replaced in four patients (7%) receiving antimicrobial therapy and in six patients (10%) who had completed antimicrobial therapy. One of the 10 valves taken for culture at surgery was positive, but only for microorganisms that were different from the microorganism isolated before the treatment. The treatment had to be interrupted in four patients because of drug allergy. Other side effects were mild except for two cases of reversible neutropenia. The treatment was easy to administer: 27 patients (46%) had no permanent intravenous catheter at any time, seven patients (12%) had such a catheter for less than 4 days. Twenty-three patients (39%) were discharged from the hospital less than 2 weeks after admission. <h3>Conclusions.</h3> —Ceftriaxone sodium administered at a once-daily dose of 2 g appears to be an effective and safe treatment of streptococcal endocarditis. In hospitals, this agent may be more convenient to administer than penicillin G with or without aminoglycosides. Some patients may even be treated as outpatients. (<i>JAMA</i>. 1992;267:264-267)
Brain Infarction and the Clinical Expression of Alzheimer Disease&lt;subtitle&gt;The Nun Study&lt;/subtitle&gt;
Authors: David A. Snowdon
Journal: JAMA (1997)

<h3>Objective.</h3> —To determine the relationship of brain infarction to the clinical expression of Alzheimer disease (AD). <h3>Design.</h3> —Cognitive function and the prevalence of dementia were determined for participants in the Nun Study who later died. At autopsy, lacunar and larger brain infarcts were identified, and senile plaques and neurofibrillary tangles in the neocortex were quantitated. Participants with abundant senile plaques and some neurofibrillary tangles in the neocortex were classified as having met the neuropathologic criteria for AD. <h3>Setting.</h3> —Convents in the Midwestern, Eastern, and Southern United States. <h3>Participants.</h3> —A total of 102 college-educated women aged 76 to 100 years. <h3>Main Outcome Measures.</h3> —Cognitive function assessed by standard tests and dementia and AD assessed by clinical and neuropathologic criteria. <h3>Results.</h3> —Among 61 participants who met the neuropathologic criteria for AD, those with brain infarcts had poorer cognitive function and a higher prevalence of dementia than those without infarcts. Participants with lacunar infarcts in the basal ganglia, thalamus, or deep white matter had an especially high prevalence of dementia, compared with those without infarcts (the odds ratio [OR] for dementia was 20.7,95% confidence interval [95% CI], 1.5-288.0). Fewer neuropathologic lesions of AD appeared to result in dementia in those with lacunar infarcts in the basal ganglia, thalamus, or deep white matter than in those without infarcts. In contrast, among 41 participants who did not meet the neuropathologic criteria for AD, brain infarcts were only weakly associated with poor cognitive function and dementia. Among all 102 participants, atherosclerosis of the circle of Willis was strongly associated with lacunar and large brain infarcts. <h3>Conclusion.</h3> —These findings suggest that cerebrovascular disease may play an important role in determining the presence and severity of the clinical symptoms of AD.
The Impact of Fraudulent Research on the Scientific Literature
Authors: Eugene Garfield
Journal: JAMA (1990)

The goal of this study was to determine the research impact of scientific fraud through citation analysis of 20 Breuning publications, using the 1980 to 1988<i>Science Citation Index and Social Sciences Citation Index</i>. These publications received 200 citations, of which 80 (40.0%) were self-citations by Breuning or his coauthors. Tracked over time, non—self-citations declined sharply in 1986 and later years, coinciding with disclosure of Breuning's fraud. The data indicated that, in this case, researchers effectively shunned work known to be or even suspected of being falsified. Unique citation contexts (101) were examined to see how citing authors used Breuning's work: 33 were negative (disagreed with findings/methods), 10 positive (agreed), and 58 neutral (no valuation). Also, 63 were inconsequential (no influence on the citing author's analysis/conclusion). Thirty-eight were material, but 21 of these led to negative conclusions. These data diminish the apparent impact of Breuning's work suggested by total citations alone. (<i>JAMA</i>. 1990;263:1424-1426)
Treatment of Hypertension With Spironolactone
Authors: Robert L. Wolf
Journal: JAMA (1966)

A double-blind study of patients with essential hypertension was performed in order to determine which dosage of spironolactone (25 mg, 100 mg, or 200 mg daily), with or without hydrochlorothiazide, had the optimum hypotensive effect. The data were analyzed by two different statistical methods, in each of which multivariate analysis of variance was used. Both methods led to the conclusion that the most efficacious treatment regimen tested was spironolactone at a daily dosage of 100 mg, without hydrochlorothiazide.
Genetic analysis of novel avian A(H7N9) influenza viruses isolated from patients in China, February to April 2013
Authors: T Kageyama, S Fujisaki, E Takashita, H Xu, S Yamada, Y Uchida, G Neumann, T Saito, Y Kawaoka, M Tashiro
Journal: Eurosurveillance (2013)

Novel influenza viruses of the H7N9 subtype have infected 33 and killed nine people in China as of 10 April 2013. Their haemagglutinin (HA) and neuraminidase genes probably originated from Eurasian avian influenza viruses; the remaining genes are closely related to avian H9N2 influenza viruses. Several characteristic amino acid changes in HA and the PB2 RNA polymerase subunit probably facilitate binding to human-type receptors and efficient replication in mammals, respectively, highlighting the pandemic potential of the novel viruses.
Pirfenidone in idiopathic pulmonary fibrosis
Authors: H. Taniguchi, M. Ebina, Y. Kondoh, T. Ogura, A. Azuma, M. Suga, Y. Taguchi, H. Takahashi, K. Nakata, A. Sato, M. Takeuchi, G. Raghu, S. Kudoh, T. Nukiwa
Journal: European Respiratory Journal (2009)

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease without proven effective therapy. A multicentre, double-blind, placebo-controlled, randomised phase III clinical trial was conducted in Japanese patients with well-defined IPF to determine the efficacy and safety of pirfenidone, a novel antifibrotic oral agent, over 52 weeks. Of 275 patients randomised (high-dose, 1,800 mg·day −1 ; low-dose, 1,200 mg·day −1 ; or placebo groups in the ratio 2:1:2), 267 patients were evaluated for the efficacy of pirfenidone. Prior to unblinding, the primary end-point was revised; the change in vital capacity (VC) was assessed at week 52. Secondary end-points included the progression-free survival (PFS) time. Significant differences were observed in VC decline (primary end-point) between the placebo group (-0.16 L) and the high-dose group (-0.09 L) (p = 0.0416); differences between the two groups (p = 0.0280) were also observed in the PFS (the secondary end-point). Although photosensitivity, a well-established side-effect of pirfenidone, was the major adverse event in this study, it was mild in severity in most of the patients. Pirfenidone was relatively well tolerated in patients with IPF. Treatment with pirfenidone may decrease the rate of decline in VC and may increase the PFS time over 52 weeks. Additional studies are needed to confirm these findings.
Health digital twins as tools for precision medicine: Considerations for computation, implementation, and regulation
Authors: Kaushik P. Venkatesh, Marium M. Raza, Joseph C. Kvedar
Journal: npj Digital Medicine (2022)

Health digital twins are defined as virtual representations ("digital twin") of patients ("physical twin") that are generated from multimodal patient data, population data, and real-time updates on patient and environmental variables. With appropriate use, HDTs can model random perturbations on the digital twin to gain insight into the expected behavior of the physical twin-offering groundbreaking applications in precision medicine, clinical trials, and public health. Main considerations for translating HDT research into clinical practice include computational requirements, clinical implementation, as well as data governance, and product oversight.
Benzimidazole and its derivatives as cancer therapeutics: The potential role from traditional to precision medicine
Authors: Yeuan Ting Lee, Yi Jer Tan, Chern Ein Oon
Journal: Acta Pharmaceutica Sinica B (2022)

Cancer is the second leading cause of mortality globally which remains a continuing threat to human health today. Drug insensitivity and resistance are critical hurdles in cancer treatment; therefore, the development of new entities targeting malignant cells is considered a high priority. Targeted therapy is the cornerstone of precision medicine. The synthesis of benzimidazole has garnered the attention of medicinal chemists and biologists due to its remarkable medicinal and pharmacological properties. Benzimidazole has a heterocyclic pharmacophore, which is an essential scaffold in drug and pharmaceutical development. Multiple studies have demonstrated the bioactivities of benzimidazole and its derivatives as potential anticancer therapeutics, either through targeting specific molecules or non-gene-specific strategies. This review provides an update on the mechanism of actions of various benzimidazole derivatives and the structure‒activity relationship from conventional anticancer to precision healthcare and from bench to clinics.
Functional Divergence in a Multi-gene Family Is a Key Evolutionary Innovation for Anaerobic Growth in <i>Saccharomyces cerevisiae</i>
Authors: David J Krause, Chris Todd Hittinger
Journal: Molecular Biology and Evolution (2022)

Abstract The amplification and diversification of genes into large multi-gene families often mark key evolutionary innovations, but this process often creates genetic redundancy that hinders functional investigations. When the model budding yeast Saccharomyces cerevisiae transitions to anaerobic growth conditions, the cell massively induces the expression of seven serine/threonine-rich anaerobically-induced cell wall mannoproteins (anCWMPs): TIP1, TIR1, TIR2, TIR3, TIR4, DAN1, and DAN4. Here, we show that these genes likely derive evolutionarily from a single ancestral anCWMP locus, which was duplicated and translocated to new genomic contexts several times both prior to and following the budding yeast whole genome duplication (WGD) event. Based on synteny and their phylogeny, we separate the anCWMPs into four gene subfamilies. To resolve prior inconclusive genetic investigations of these genes, we constructed a set of combinatorial deletion mutants to determine their contributions toward anaerobic growth in S. cerevisiae. We found that two genes, TIR1 and TIR3, were together necessary and sufficient for the anCWMP contribution to anaerobic growth. Overexpressing either gene alone was insufficient for anaerobic growth, implying that they encode non-overlapping functional roles in the cell during anaerobic growth. We infer from the phylogeny of the anCWMP genes that these two important genes derive from an ancient duplication that predates the WGD event, whereas the TIR1 subfamily experienced gene family amplification after the WGD event. Taken together, the genetic and molecular evidence suggests that one key anCWMP gene duplication event, several auxiliary gene duplication events, and functional divergence underpin the evolution of anaerobic growth in budding yeasts.
Assessing the Impact of the American Heart Association’s Research Portfolio: A Scientific Statement From the American Heart Association
Authors: Mark A. Creager, Adrian F. Hernandez, Jeffrey R. Bender, Mary H. Foster, Paul A. Heidenreich, Steven R. Houser, Donald M. Lloyd-Jones, William H. Roach, Véronique L. Roger
Journal: Circulation (2022)

A task force composed of American Heart Association (AHA) Research Committee members established processes to measure the performance of the AHA's research portfolio and evaluated key outcomes that are fundamental to the overall success of the program. This report reviews progress that the AHA research program has had in achieving its goals relevant to the research programs in the AHA's research portfolio from 2008 to 2017. Comprehensive performance metrics were identified to assess the impact of AHA funding on researchers' career progress and research outcomes. Metrics included bibliometric analysis (ie, tracking of publications and their impact) and career development measures (ie, subsequent grant funding, intellectual property, faculty appointment/promotion, or industry position). Publication rates ranged from ≈0.5 to 4 publications per year, with a strong correlation between number of publications per year and later career stage. The Field-Weighted Citation Index, a metric of bibliometric impact, was between 1.5 and 3.0 for all programs, indicating that AHA awardee publications had a higher citation impact compared with similar publications. To gain insight into the career progression of AHA awardees, a 2-year postaward survey was distributed. Of the Postdoctoral Fellowship recipient respondents, 72% obtained academic research positions, with the remaining working in industry or government research settings; 72% of those in academic positions obtained additional funding. Among respondents who were Beginning Grant-in-Aid and Scientist Development Grant awardees, 45% received academic promotions and 83% obtained additional funding. Measuring performance of the AHA's research portfolio is critical to ensure that its strategic goals are met and to show the AHA's commitment to high-quality, impactful research.
LncRNA PSR Regulates Vascular Remodeling Through Encoding a Novel Protein Arteridin
Authors: Junyi Yu, Wei Wang, Jining Yang, Ye Zhang, Xue Gong, Hao Luo, Nian Cao, Zaicheng Xu, Miao Tian, Peili Yang, Qiao Mei, Zhi Chen, Zhuxin Li, Chuanwei Li, Xudong Duan, Qing Rex Lyu, Chen Gao, Bing Zhang, Yibin Wang, Gengze Wu, Chunyu Zeng
Journal: Circulation Research (2022)

Vascular smooth muscle cells (VSMCs) phenotype switch from contractile to proliferative phenotype is a pathological hallmark in various cardiovascular diseases. Recently, a subset of long noncoding RNAs was identified to produce functional polypeptides. However, the functional impact and regulatory mechanisms of long noncoding RNAs in VSMCs phenotype switching remain to be fully elucidated.
Groin and buttocks involvement and methicillin-resistant Staphylococcus aureus nasal swab independently predict cutaneous abscess and methicillin-resistant Staphylococcus aureus infection in inpatient pediatric cellulitis: A retrospective cohort study
Authors: Sidharth Chand, Renajd Rrapi, Colleen K. Gabel, Chadi El Saleeby, Daniela Kroshinsky
Journal: Journal of the American Academy of Dermatology (2022)
Outcomes at least 90 days since onset of myocarditis after mRNA COVID-19 vaccination in adolescents and young adults in the USA: a follow-up surveillance study
Authors: Ian Kracalik, Matthew E Oster, Karen R Broder, Margaret M Cortese, Maleeka Glover, Karen Shields, C Buddy Creech, Brittney Romanson, Shannon Novosad, Jonathan Soslow, Emmanuel B Walter, Paige Marquez, Jeffrey M Dendy, Jared Woo, Amy L Valderrama, Alejandra Ramirez-Cardenas, Agape Assefa, M Jay Campbell, John R Su, Shelley S Magill, David K Shay, Tom T Shimabukuro, Sridhar V Basavaraju, Paula Campbell, Chidera Anugwom, Colenda Arvelo Jefferson, Kimberly Badger, Nastocia Bafford, Chandra Barnes, Stephanie Boles, Emory Collins, Mitesh Desai, Theresa Dulski, Barbara Dyleski, Kathryn Edwards, Melanie Feyereisen, Stephanie Gonsahn, Tchernavia Gregory, Jyothi Gunta, Kara Jacobs Slifka, Charlotte Kabore, Bryan K. Kapella, Susan Karol, Kalah Kennebrew, Nancy Kluisza, Sean Lang, Labretta Lanier Gholston, Marcella Law, Jennifer Lehman, Jacek M. Mazurek, Henraya McGruder, Kiara McNamara, Maria-Luisa Moore, Pedro Moro, John F. Moroney, Oidda Museru, Cassandra Nale, Andi Neiman, Kim Newsome, Erika Odom, Brooke Pantazides, Suchita Patel, Agam Rao, Laura Reynolds, Sonya Robinson, Frederick L. Ruberg, Tammy Schaeffer, Dipesh Solanky, Laurence Sperling, Toscha Stanley, Regina Sullivan, Allan Taylor, Kimberly Thomas, Shayle Thompson, Jigsa Tola, Cuc H. Tran, Steven Wiersma, Kimberly Works
Journal: The Lancet Child & Adolescent Health (2022)
Faecal microbiota transplantation for first or second Clostridioides difficile infection (EarlyFMT): a randomised, double-blind, placebo-controlled trial
Authors: Simon Mark Dahl Baunwall, Sara Ellegaard Andreasen, Mette Mejlby Hansen, Jens Kelsen, Katrine Lundby Høyer, Nina Rågård, Lotte Lindgreen Eriksen, Sidsel Støy, Tone Rubak, Else Marie Skjøde Damsgaard, Susan Mikkelsen, Christian Erikstrup, Jens Frederik Dahlerup, Christian Lodberg Hvas
Journal: The Lancet. Gastroenterology & hepatology (2022)
Effect of marijuana smoking on lung function change in older ever tobacco smokers
Authors: Igor Barjaktarevic, Christopher B. Cooper, Tracie Shing, Russell G. Buhr, Eric A. Hoffman, Prescott G. Woodruff, M. Bradley Drummond, Richard E. Kanner, MeiLan K. Han, Nadia N. Hansel, Russell P. Bowler, Gregory L. Kinney, Sean Jacobson, Madeline A. Morris, Fernando J. Martinez, Jill Ohar, David Couper, Donald P. Tashkin
Journal: European Respiratory Journal (2022)

<b>This cohort study of tobacco smokers with COPD failed to demonstrate any clinically significant association of current/former marijuana smoking of any cumulative lifetime amount with a worsening trajectory of FEV<sub>1</sub> over an average of approximately 5 years</b> https://bit.ly/3ISoc2c
Case-finding and diagnosis of obstructive airway diseases: the Dragons’ Den experience
Authors: Ian D. Pavord
Journal: European Respiratory Journal (2022)

There is increasing concern about a stalling of progress against key outcomes in obstructive airway disease over the last 10–15 years [1, 2]. Addressing this is an important priority for healthcare systems struggling with rising costs and huge winter bed pressures, to which obstructive airway diseases make an important and growing contribution. The UK government's response has been to announce a 10-year life sciences mission in respiratory medicine to focus on preventing, diagnosing, monitoring and treating common diseases early [3]. The goal is to reduce mortality and morbidity from respiratory disease in the UK and globally. Airway disease diagnosis: earlier intervention to modify natural history of obstructive airway diseases <https://bit.ly/3LVxdYK> The National Institute of Health and Social Care Research for Biomedical Research Centre funding. Nayia Petousi and Simon Couillard for helpful comments. Any similarities with a bruising conversation the author has recently had with the members of the UK government who are driving the Respiratory Mission are intentional!
Atenolol treatment does not affect behavioral outcomes in pediatric patients with infantile hemangiomas: A case-control cohort study
Authors: Fareed Sabbah, Ilan Shamir, Lidia V Gabis, Ayelet Ollech, Meirav Shaham, Aviv Barzilai, Sharon Baum, Orit Krispin, Tamar Peleg, Dan Ben Amitai, Shoshana Greenberger
Journal: Journal of the American Academy of Dermatology (2022)